Robert C. Andersen

Long-term results and complications in renal transplant recipients. Observations in the second decade.

In this study, we analyzed the incidence of complications and clinical results of 57 patients who received kidney transplants at our institution and survived with a functioning allograft for 10 years or longer. All patients received their care at our center and their clinical and laboratory data were monitored routinely at minimum monthly intervals. In this second decade, during a mean follow-up of 2.8 +/- 2.2 years (range 0.4-7.8 years), 7 patients suffered graft loss (chronic rejection 6; irreversible acute tubular necrosis from aminoglycosides 1) and 7 others died with a functioning allograft (causes: hepatic failure 2, sepsis 2, malignancy 2, and cardiac infarction 1). The cumulative patient survival was 96% at 11 years and 85% at 15 years. The corresponding graft survival rate was 92% at 11 years and 71% at 15 years. Of the 43 patients currently followed, 38 are fully rehabilitated, 4 are partially rehabilitated, and 1 is medically disabled. The complications observed were: infection in 25 patients (44%), hypertension in 24 (42%), hyperlipidemia in 23 (40%), liver disease, 22 (39%) musculoskeletal problems in 21 (37%), cataracts in 19 (33%), rejection in 15 (26%), malignancy in 9 (16%), vascular occlusive disease in 9 (16%), gastrointestinal disorders in 9 (16%), and other problems not included in the above categories in 26 (46%). Our observations suggest that renal transplant recipients experience significant morbidity and mortality even in the second decade. Continued medical follow-up is therefore essential for an early diagnosis and management of these late complications. Measures directed at prevention and therapy of these late complications may further enhance the long-term success rate of renal transplantation.

The impact of diabetes on vascular complications following cadaver renal transplantation

To assess the impact of diabetes on vascular complications occurring in renal transplant recipients, we compared the incidence of vascular disease in 283 non-diabetic (ND) and 99 diabetic (D) patients who received primary cadaver renal transplants at our center between 1/1/76 and 12/31/85. The median observation time in the ND patients was 31 months, and in D patients it was 20 months. Both ND and D patients were subdivided into group A if they had preexisting clinical vascular disease and group B if they had no prior disease. The vascular complications between the ND and D patients were analyzed in 3 subsets: prevalence of vascular disease prior to renal transplantation; posttransplant recurrent vascular disease in group A; and posttransplant vascular disease, new, in group B. The results showed that, prior to renal transplantation, D patients have a higher prevalence of clinical vascular disease (33%), compared with ND patients (13%) (P = .00001). In group A, the recurrence rate of vascular disease after transplantation was also higher in D patients (67%) compared with ND patients (40%) (P = .05). In group B, the incidence of posttransplant vascular disease (new) was significantly higher in D patients (33%) compared with the ND patients (13%) (P = .002). Also, the amputation rate was significantly higher in D patients (18%) compared with ND patients (0.4%) (P = .000001). Our data suggest that morbidity from vascular disease is significantly increased in diabetic renal transplant recipients compared with nondiabetic patients. Such increased morbidity from vascular disease in the diabetic patients may also be observed in the period before renal transplantation.

Clinical impact of replacing Minnesota antilymphocyte globulin with ATGAM.

In August 1992, we replaced Minnesota antilymphocyte globulin (MALG) with lymphocyte immune globulin, antithymocyte globulin (equine) (ATGAM) in our immunosuppression protocols. The clinical impression of increased graft rejection prompted our assessment of the effect of this change on patient and graft outcome. The initial study group consisted of 426 renal transplant recipients transplanted between October 1, 1987, and September 21, 1993. After exclusions, 388 transplant events, with a minimum 8-month follow-up, made up the final study cohort: 323 patients received MALG and 65 received ATGAM. Immunosuppression included intravenous methylprednisolone, oral prednisone, oral AZA, CsA in some cases, and intravenous MALG or ATGAM, 15 mg/kg/day, for 7 to 14 days. Acute rejection was treated with high dose intravenous steroids and steroid-resistant episodes were treated additionally with either MALG or OKT3. Statistical comparisons were stratified for multiple patient characteristics and treatment variations. There was a greater incidence of rejection in general, and a higher incidence of steroid-resistant episodes requiring subsequent antilymphocyte globulin therapy (P = 0.0073) in patients receiving ATGAM versus MALG. No difference was seen in the incidence of CMV infection or blood-borne sepsis. Lymphoma occurred in 3 MALG and 2 ATGAM recipients. MALG recipients were significantly less likely to experience rejection within the first 60 days after transplant (P = 0.0127 using unstratified data; P <0.0001 when data were stratified for patient characteristics). The relative risk of acute rejection for posttransplant days 5, 7, 10, and 14 was consistently higher for ATGAM-treated patients. We conclude that MALG and ATGAM are not equivalent drugs, and that MALG is a more effective immunosuppressant, and is just as safe as ATGAM in our protocol environment.

A randomized trial comparing cyclosporine induction with sequential therapy in renal transplant recipients

Abstract Calcium antagonists may reduce the nephrotoxicity of cyclosporine (CsA), allowing CsA to be introduced immediately after renal transplantation and thereby obviating the need for sequential induction therapy with a monoclonal or polyclonal antibody. To test this hypothesis, in a pilot feasibility trial 100 cadaveric or one-haplotype-mismatched living-related renal transplant recipients were randomized to either (1) sequential therapy with antithymocyte globulin (ATG) (ATGAM; Upjohn, Kalamazoo, MI) 20 mg/kg/d for 7 to 14 days until renal function was established and CsA (Sandimmune; Sandoz, East Hanover, NJ) was started, or (2) CsA 8 mg/kg/d begun immediately before surgery with diltiazem (Cardizem; Marion Merrell Dow, Kansas City, MO) 60 mg sustained release twice daily. Acute rejection episodes during the first 90 days were not different with ATG versus CsA induction (42% v 28%; P = 0.142 by chi-square analysis). Graft failures (10% v 16%; P = 0.372) and the incidence of delayed graft function (28% v 34%; P = 0.516) were also similar with ATG compared with CsA. ATG caused lower platelet counts (138 ± 59 × 103v 197 ± 75 × 103 at 7 days; P

The Effects Of Transfusion Of Frozenthawed Deglycerolized Red Cells On Renal Graft Survival

SUMMARY In patients that received transplants of cadaver kidneys, prior transfusion improves the prognosis for graft survival. Patients receiving frozen-thawed red cells have better 1-year survival rates than patients given other forms of red cells. The effect of prior transfusions is minimal in patients that received transplants of kidneys from living related donors.

Renal secretion and hepatic clearance of human multiple renin forms.

Human active renin can be separated into at least five forms by isoelectric focusing. The present study assessed the preferential renal secretion and hepatic degradation of renin forms in humans. The renin form profile of secreted renal renin was determined before transplant in an ex vivo kidney donor perfusion system and compared with the peripheral plasma multiple renin form profile of normal subjects. The effect of hepatic degradation on renin forms was assessed in hepatic vein plasma in comparison with infrarenal vena cava plasma in hypertensive patients during renal vein renin studies. The results revealed a significantly greater proportion of the more basic forms in the perfusate of donor kidneys compared with normal plasma. In hypertensive patients the proportion of the more basic renin forms in the hepatic vein was significantly decreased in comparison with the infrarenal vena cava. Thus, the human kidney may preferentially secrete the more basic renin forms. In contrast, the liver preferentially degrades the more basic forms, giving these forms a shorter plasma half-life. The preferential secretion and clearance of the more basic forms of renin may contribute to short-term control of human renin-angiotensin system activity.

Reimplantation of the baboon lung after extended ischemia.

Thirty baboons were subjected to lung reimplantation with ischemia extended up to 4 hours with an over-all 30 day mortality rate of 33%. Heparin was not used. No vascular anastomosis thrombosed. Bronchospirometry studies frequently revealed depressed function one week after reimplantation with subsequent return of function to normal. Elevated pulmonary artery pressure after contralateral pneumonectomy was found in some baboons, but returned to normal at subsequent right heart catheterization.

Causes and Evaluation of Incipient Vascular Access Failure in Chronic Hemodialysis

The life span of a patient committed to chronic hemodialysis depends on the number of sites available for vascular access and the longevity of each site. Long-term vascular access is thus critical to success in chronic hemodialysis. To maximize the longevity of an access site, constant evaluation and appropriate care are essential ( 1-4). This communication deals with the failing of the most common forms of access: The Brescia-Cimino arteriovenous fistula and the subcutaneous conduit fistula.

Unusual transplant renal angioplasty complication: Case report

We report an avulsion of a transplant upper pole renal artery following apparently successful percutaneous transluminal angioplasty (PTA) of a stenosis involving main, upper, and lower pole renal arteries. We believe that the use of a high pressure balloon was the causative factor. If the branches at the bifurcation cannot be protected and if the stenoses fail to resolve under moderate balloon insufflation pressures (<5–6 atmospheres), consideration should be given to surgical revascularization.

A Randomized Trial Comparing Cyclosporine Induction With Sequential Therapy in Renal Transplant Recipients

Calcium antagonists may reduce the nephrotoxicity of cyclosporine (CsA), allowing CsA to be introduced immediately after renal transplantation and thereby obviating the need for sequential induction therapy with a monoclonal or polyclonal antibody. To test this hypothesis, in a pilot feasibility trial 100 cadaveric or one-haplotype-mismatched living-related renal transplant recipients were randomized to either (1) sequential therapy with anti-thymocyte globulin (ATG) (ATGAM; Upjohn, Kalamazoo, MI) 20 mg/kg/d for 7 to 14 days until renal function was established and CsA (Sandimmune; Sandoz, East Hanover, NJ) was started, or (2) CsA 8 mg/kg/d begun immediately before surgery with diltiazem (Cardizem; Marion Merrell Dow, Kansas City, MO) 60 mg sustained release twice daily. Acute rejection episodes during the first 90 days were not different with ATG versus CsA induction (42% v 28%; P = 0.142 by chi-square analysis). Graft failures (10% v 16%; P = 0.372) and the incidence of delayed graft function (28% v 34%; P = 0.516) were also similar with ATG compared with CsA. ATG caused lower platelet counts (138 +/- 59 x 10(3) v 197 +/- 75 x 10(3) at 7 days; P < 0.001) and lower white blood cell counts (9.6 +/- 4.6 x 10(3) v 12.3 +/- 4.9 x 10(3) at 7 days; P = 0.003). Diltiazem reduced the dose of CsA required to maintain target blood levels (479 +/- 189 mg/d v 576 +/- 178 mg/d at 14 days; P = 0.015). There were no statistically significant differences between the groups in serum creatinine levels at days 1, 3, 5, 7, 14, 28, 60, or 90. The results of this pilot feasibility trial suggest that prophylactic treatment with CsA and diltiazem may be equally effective and less toxic than ATG induction after renal transplantation.